1-Deoxynojirimycin inhibits metastasis of B16F10 melanoma cells by attenuating the activity and expression of matrix metalloproteinases-2 and -9 and altering cell surface glycosylation

J Agric Food Chem. 2010 Aug 25;58(16):8988-93. doi: 10.1021/jf101401b. Epub 2010 Jul 22.

Abstract

1-Deoxynojirimycin (1-DNJ), an iminosugar rich in mulberry, has been shown to possess antimetastatic potential. The antimetastatic mechanisms of 1-DNJ in melanoma B16F10 cells were studied, as were the antimetastatic activity (cell adhesion, migration, and invasion) of 1-DNJ, matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) mRNA, and flow cytometric analysis of cell surface in melanoma B16F10 cells. 1-DNJ significantly inhibited invasion, migration, and cell-matrix adhesion and markedly decreased MMP-2 and MMP-9 activity and mRNA expression. In contrast, 1-DNJ effectively enhanced the expression of TIMP-2 mRNA. In addition, 1-DNJ significantly decreased abnormal glycosylation and/or sialylation on B16F10 melanoma cell surface but increased the levels of α-mannose. Thus, the antimetastatic effects of 1-DNJ against B16F10 melanoma cells are likely associated with its attenuated activities and expression of MMP-2/9, enhancement of the TIMP-2 mRNA expression, and alterations of the cell surface-binding motif. These results suggest that 1-DNJ may be useful as an adjuvant of antimetastatic agents such as cisplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / pharmacology*
  • Animals
  • Base Sequence
  • Cell Membrane / metabolism
  • DNA Primers
  • Glycosylation
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / enzymology
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Neoplasm Metastasis / prevention & control*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • DNA Primers
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • 1-Deoxynojirimycin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9